We are developing a suite of new computational methods to predict disposition of therapeutic agents directly injected into brain parenchyma. Our broad purpose is to develop a systems approach to site-specific delivery for brain diseases. We expect use in device design and selection, animal and pre-clinical testing, pre-operative planning, intra-operative controlled delivery, and post-operative monitoring. This fast track application aims to create (i) methods to validate models via in-vivo imaging (in Phase I), and (ii) a software product that can be used for predicting spatial distribution of intra-parenchymally injected molecules (in Phase II). The specific aims in Phase I are: (1) investigate MRI methods that can accurately assess the concentration of contrast agents in tissue when increase of water content and tissue edema can make quantitation difficult; and (2) propose methods to assess the resistance of brain tissue to the flow of injected fluid, including preferred directions of flow. Successful completion will enable assay of molecules in tissue in vivo for research. This will therefore have value well beyond the other aim, namely to provide the basis for validating software which will be developed in Phase II to serve as a critical pre-operative planning tool for all such deliveries in clinical practice.